OVERALL : ABSTRACT This is the third competing continuation for an accomplished Environmental Health Sciences Core Center (EHS CC), The Center of Excellence in Environmental Toxicology (CEET) at the University of Pennsylvania (Penn). The Director is Trevor M. Penning, PhD (The Thelma Brown and Henry Charles Molinoff Professor of Pharmacology) and the Deputy Director is Rebecca A. Simmons, MD (The Hallam Hurt Endowed Professor in Pediatrics). The Center is comprised of 71 members from 18 Departments and 5 Schools, with almost equal representation of basic and clinician-scientists drawn from the Perelman School of Medicine (PSOM) and Children?s Hospital of Philadelphia (CHOP). The CEET has built an institutional, regional and national identity in environmental health sciences (EHS) in the absence of a School of Public Health and Department of EHS at Penn. The synergistic combination of basic and clinician-scientists within the CEET promotes translational environmental health research that addresses fundamental questions and translates knowledge into action to have a major impact on human health and disease consistent with the NIEHS Strategic Plan. The CEET mission is to ?elucidate the mechanistic links between environmental exposures and human disease, and translate findings into action to improve the health of vulnerable individuals, and local, national, and global communities?. This mission is accomplished through five aims. In Aim 1: We use a flexible thematic area structure to conduct translational environmental health research to improve precision public health. Our current themes are in Air Pollution & Lung Health; Environmental Exposures & Cancer; Windows-of- Susceptibility; and Environmental Neuroscience. Each thematic area integrates the pillars or exposure science, adverse outcome constructs (pathways and networks) to explain the phenome with translation to communities and human subjects. In Aim 2: We conduct bi-directional communication with communities in S.E and N.E. Pennsylvania and use community engagement to set the research agenda for the CEET. In Aim 3: We provide a facility core structure to promote precision public health. Our Integrative Health Sciences Facility Core is adept in human subject study design and in conducting population exposure services, using cartographic modeling, GIS tools and biosensors. Biomarkers of exposure and effect are measured in our Translational Biomarker Core which conducts mass spectrometric assays at a level of precision and accuracy difficult to emulate elsewhere. The Exposure Biology Informatics Core brings to bear the power of computation, machine learning and AI to predict the toxicity of unknowns and integrate Big-data sets to recognize patterns in ?omics? data and predict adverse outcomes. In Aim 4: We build capacity in environmental health sciences by funding pilot projects to Early Stage Investigators (ESI) and to senior investigators conducting environmental health research for the first time. In Aim 5: We cultivate the careers of ESI through a transformative Environmental Health Scientist Support Program that provides mentoring, grant proposal review, environmental health and Facility Core workshops.